The biogenesis and assembly of a respiratory competent mitochondrion results from the joint expression of two distinct genetic systems, mitochondrial and cytoplasmic, composed of two discrete genomes and two physically separated protein synthetic systems. As yet, the means by which the expression of these two genetic systems is coordinated is unclear. In this study, yeast cytochrome c oxidase, a definable entity of the inner mitochondrial membrane which is composed of polypeptide subunits translated on both protein synthetic systems, is proposed as a prototype system with which to study this coordination. Subunit-specific antisera and purified subunits will be used to study (1) the time of synthesis of both sets of subunits during the cell cycle, (2) the role of post translational processing in subunit interaction and enzyme assembly, and (3) the stimulatory effects of cytoplasmic translation products on the in vitro translation of mitochondrially-made subunits. These studies will be complemented by chemical experiments aimed at identifying the function of each subunit and reconstitution experiments designed to assess the role of hydrophobic mitochondrially-made subunits in enzyme assembly and in the binding of the hydrophilic cytoplasmically-made subunits to the inner mitochondrial membrane. BIBLIOGRAPHIC REFERENCES: Poyton, R.O. and G.S.P. Groot, 1975. Biosynthesis of polypeptides of cytochrome c oxidase by isolated mitochondria. Proc. Natl. Acad. Sic. (U.S.A.) 72, 172-76. Groot, G.S.P. and R.O. Poyton. 1975. Oxogen control of cytochrome c oxidase synthesis in isolated mitochondria from Saccharomyces cerevisiae. Nature 255, 238-40.